METHOD AND SYSTEM FOR CALCULATING A QUANTIFICATION INDICATOR OF A DERMAL REACTION IN THE SKIN OF A LIVING BEING

Abstract

This calculation method is intended to calculate a quantification indicator for a dermal reaction in the skin of a living being, the skin containing a plurality of chromophores. The method comprises illuminating (100) a skin area to be characterized with a light beam from a light source, the area to be characterized containing the dermal reaction, and measuring (110), using a spectrometer, the spectrum of backscattered radiation from the skin following the illumination of said area to be characterized. The method also comprises determining (120), from the measured spectrum and for at least a given value of the wavelength of the light beam, a value for the absorption coefficient of the area to be characterized, and calculating (130), from the determined value(s) of the absorption coefficient, the concentration of at least one skin chromophore.The method finally includes calculating (140) the quantification indicator as a function of the previously calculated concentration of the chromophore(s). The method further includes determining (120), from the measured spectrum and for at least one given value of the wavelength of the light beam, a value of the scattering coefficient of the area to be characterized, and the quantification indicator of the dermal reaction is calculated also as a function of the determined value(s) of the scattering coefficient.

Description

In Figure 4, the sheets 200, 205, 210, 215, 220 and 225 then correspond to the predetermined reflectances RLuT,Di for the six distinct predetermined distances D, the sheet 200 corresponding to the predetermined reflectance Rlut.di for the smallest distance Di among said distances Di5 and the sheet 225 corresponding to the predetermined reflectance Rluldn for the largest distance DN among said distances Dj. It is then also observed that the greater the distance between the excitation fiber 24 and the corresponding detection fiber 26, the lower the amplitude of the reflectance R. The sheet 230 corresponds to the reflectance R obtained for the excitation return 27. During the determination step 120, the pair of determined values ​​of the absorption coefficient pa and the diffusion coefficient ps is then that minimizing the error between the predetermined reflectances RLut of the reference table LUT and the reflectance value(s) Rmesure measured for a given value of the wavelength λ. The pair of determined values ​​of the absorption coefficient pa and the diffusion coefficient ps verifies, for example, the following equation: JN ^RLbT-R—Ÿ (18) / —1 Figure 4 illustrates as an example the determination of the torque (pa, ps) obtained for the wave value Ào, this being then noted (na(À0), ns(À0))- This determination step 120 is repeated for each of the values ​​of the wavelength K in the predetermined interval and according to the predetermined sampling step, following the values ​​described previously. The concentration of at least one chromophore of the skin is then calculated, during step 130, from the or each determined value of the absorption coefficient pa(À) and using the first calculation software 38. The absorption coefficient pa(À) verifies the following equation: Ai (^) = ^eOXP'ahb (^) + Ox^ahhCn (^) + ^f^aeau (^) + RRf^aBil (^) + Ra^^aFat (^) + Repi ^dem: * ^e^aMel (^) (19) where Deox represents the concentration of deoxyhemoglobin in the corresponding zone ZC, ZS of the skin 12, Ox represents the concentration of oxyhemoglobin in said area of ​​the skin 12, W represents the concentration of water in said area of ​​the skin 12, Bil represents the concentration of bilirubin in said area of ​​the skin 12, Fat represents the concentration of fat in said area of ​​the skin 12, and Mel represents the fraction of melanosomes present in an epidermis of thickness Lepi assumed to be equal to 60 pm for a total thickness of dermis Lderm assumed to be equal to 1.5 mm. Let us specify that the terms Pahb(^)! ùahbO2 (\), Paeau(^)! ùaBil(^)! PaFat^) and PaMel(^) represent respectively the absorption coefficients of deoxyhemoglobin, oxyhemoglobin, water, bilirubin and fat for a unit concentration. The or each chromophore is selected from the group consisting of: water, melanin, oxyhemoglobin, deoxyhemoglobin and bilirubin, the oxyhemoglobin concentration HbO2 and the deoxyhemoglobin concentration Hb being preferably calculated. The concentrations of bilirubin Bil and fat Fat are, for example, not taken into account, the quantities BiLpaBii and Fat.paFat being assumed to be negligible for wavelength values ​​λ between 400 nm and 1000 nm. In other words, the contribution of bilirubin and fat to absorption is considered negligible compared to the other chromophores for this range of wavelength values ​​λ, for the dermal reaction studied. In addition, during step 130 of calculating the concentration of the chromophore(s) HbO2, Hb, the concentration of the chromophore(s) HbO2, Hb is first calculated for the healthy zone ZS of the skin 12, visible in FIG. 1, from the value(s) of the absorption coefficient pa of said healthy zone ZS, and the concentration of the chromophore(s) HbO2, Hb is then calculated for the zone to be characterized ZC from the concentration of the chromophore(s) for the healthy zone ZS and the value(s) of the absorption coefficient pa of said zone to be characterized ZC. In Figure 5, curve 300 represents the values ​​taken by the diffusion coefficient ps of the healthy zone ZS for the values ​​of the wavelength λ between 400 nm and 900 nm, and curve 310 represents the values ​​taken by the diffusion coefficient ps of the zone to be characterized ZC for the same interval of values ​​of the wavelength λ. In Figure 6, curve 350 represents the values ​​taken by the absorption coefficient pa of the healthy zone ZS for the values ​​of the wavelength λ between 400 nm and 900 nm, and curve 360 ​​represents the values ​​taken by the absorption coefficient pa of the zone to be characterized ZC for the same interval of values ​​of the wavelength λ. According to this supplement, steps 100, 110 and 120 described previously are then carried out firstly for the healthy zone ZS, then secondly for the zone to be characterized ZC. The oxyhemoglobin concentration HbO2, the deoxyhemoglobin concentration Hb, the melanin concentration Mel and the water concentration W are first calculated, using the first calculation software 38, for the healthy zone ZS from the values ​​of the absorption coefficient pa of said healthy zone ZS and standard initial values ​​of the oxyhemoglobin concentrations HbO2, deoxyhemoglobin Hb, melanin concentration Mel and the water concentration W. These standard values ​​are for example taken from the literature. Assuming that the quantity Mel.paMei does not vary between the healthy zone ZS and the zone to be characterized ZC, the oxyhemoglobin concentration HbO2 and the deoxyhemoglobin concentration Hb are then calculated, using the first calculation software 38, for the zone to be characterized ZC from the values ​​of the absorption coefficient pa of said zone to be characterized ZC and initial values ​​of the concentrations equal to the last values ​​calculated previously for the healthy zone ZS. The initialization of the algorithm from values ​​from the healthy zone ZS allows better consideration of the individual's phototype. The IND indicator for quantifying the skin reaction is finally calculated, during step 140, using the second calculation software 40 and as a function of the concentration of the or each chromophore HbO2, Hb previously calculated and also as a function of the or each determined value of the diffusion coefficient ps of the zone to be characterized ZC. The quantification indicator IND is preferably calculated as a function of an average, such as the arithmetic average, of a plurality of values ​​of the diffusion coefficient ps of the zone to be characterized ZC, these values ​​of the diffusion coefficient ps being determined for a plurality of values ​​of the wavelength λ, for example between 450 nm and 800 nm, preferably between 650 nm and 800 nm, more preferably between 740 nm and 760 nm. The quantization indicator IND then verifies, for example, the following equation: IND = Ch + Pt x Ox + Yi x Deox + Ôt x Dif (20) where IND represents the quantification indicator of the dermal reaction, Ch, p1; Yi and Ô! are predetermined coefficients for a given value of the delay between the instant of measurement of the spectrum M of the backscattered radiation and the instant of injection of the active principle, with Pi, Yi and Ôt of non-zero values, Dif represents the average, such as the arithmetic mean, of the determined value(s) of the diffusion coefficient ps calculated for the wavelength intervals indicated above, namely [450 nm; 800 nm], preferably [650 nm; 800 nm], and more preferably [740 nm; 760 nm]. The values ​​of the coefficients ch, Pi, Yi and are, for example, predetermined empirically from tests carried out on a set of patients. This predetermination is preferably done via discriminant factor analysis. Alternatively, the predetermination is done via principal component analysis. Alternatively, the quantification indicator IND is calculated as a function of a difference between the concentrations of the or each chromophore Hb, HbO2 of the healthy zone ZS and the zone to be characterized ZC and as a function of the difference(s) between the determined values ​​of the diffusion coefficient ps of the healthy zone ZS and the zone to be characterized ZC. According to this variant, the quantification indicator IND then verifies, for example, the following equation: IND = + p^ x AOx + y'i x ADeox + x ADif (21) where IND represents the quantification indicator of the dermal reaction, cG, P'15 y'i and 5^ are predetermined coefficients for a given value of the delay between the instant of measurement of the spectrum M of the backscattered radiation and the instant of injection of the active principle, with P'i, y'i and ô't of non-zero values △Ox and ADeox represent a difference between the oxyhemoglobin HbO2 concentrations of the healthy zone ZS and the zone to be characterized ZC, and respectively a difference between the deoxyhemoglobin Hb concentrations of the healthy zone ZS and the zone to be characterized ZC, and △It represents an average, such as the arithmetic mean, of the deviation(s) between the determined values ​​of the diffusion coefficient ps of the healthy zone ZS and of the zone to be characterized ZC, the average being for example calculated for the wavelength intervals indicated above, namely [450 nm; 800 nm], preferably [650 nm; 800 nm], and more preferably [740 nm; 760 nm]. Similarly, the values ​​of the coefficients cG, P'15 y1! and are, for example, predetermined empirically from tests carried out on a set of patients. For example, for a tuberculin test, the values ​​of the coefficients a'^ P'15 Y't and are respectively equal to 1.741, -0.007, -0.147 and -0.434, as will be described later for equation (23). The results obtained with the state-of-the-art method for a group of 48 patients during clinical trials are illustrated on the histogram in Figure 7 representing, in the form of bars 400, the values ​​of the quantification indicator IND calculated for each of the 48 tests on patients, the tests being identified by respective numbers varying on the abscissa from 1 to 48. In the example in Figure 7, the quantification indicator IND verifies the following equation: IND = -0.070 - 0.128 x Ox - 0.026 x Deox (22) We then note the presence of numerous diagnostic errors for the skin reaction test, namely cases where the reaction is wrongly indicated as positive (false positive), the bars then being referenced 400A, and conversely cases where the reaction is indicated as negative when it is in reality positive (false negative), the bars then being referenced 400B. In the example in Figure 7, 17 cases of false positive and 3 cases of false negative are counted, i.e. 20 errors for 48 tests, i.e. an error rate equal to 42%. In comparison, the results obtained with the method according to the invention for the same group of 48 tests on patients are illustrated on the histogram of figure 8 representing in the form of bars 500 the values ​​of the quantification indicator IND calculated for each of said tests, also identified by respective numbers varying on the abscissa from 1 to 48. The results of figure 8 correspond to the case where the quantification indicator IND is calculated according to equation (21). In the example of figure 8, the quantification indicator IND verifies the following equation: IND = 1.741 - 0.007 x AOx - 0.147 x ADeox - 0.434 x ADif (23) It can then be seen that the number of diagnostic errors is much lower with the method according to the invention than with the method of the state of the art. Indeed, in the example of Figure 8, only 5 errors are counted for 48 tests, i.e. an error rate equal to 10%, that is to say substantially 4 times less than the error rate of the state of the art. The errors in this example are 4 cases of false positive, the bars then being referenced 500A, and 1 case of false negative, said bar being referenced 500B. In the example of Figures 7 and 8, the IND quantification indicators are calculated 72 hours after the stimulation causing the dermal reaction. It was then found that it is possible to calculate the quantification indicator IND in less than 72 hours using the calculation method according to the invention, while maintaining a low error rate. Thus, sufficiently reliable indicators could be established, allowing earlier quantification of the reaction, the time between injection and reading being able to be reduced to 18 hours. With the method according to the invention, taking into account the diffusion coefficient ps in the calculation of the quantification indicator IND makes it possible in particular to better detect an induration. It was further found that the results obtained are better when the quantification indicator IND is calculated from equation (21), rather than from equation (20). It is then understood that the method and the calculation system 10 according to the invention make it possible to improve the relevance of the calculated quantification indicator IND, while making it possible to calculate this indicator IND more quickly after the stimulation at the origin of the dermal reaction. Figure 9 corresponds to a second embodiment for which the elements identical to the first embodiment described previously are identified by identical references, and are not described again. According to this second embodiment, the second calculation software 40 is capable of calculating the quantification indicator IND as a function of the concentration of the or each chromophore previously calculated, of the or each determined value of the diffusion coefficient ps, and also as a function of the or each determined value of the absorption coefficient pa. Alternatively, the second calculation software 40 is capable of calculating the quantification indicator IND as a function of a difference between the concentrations of the or each chromophore Hb, HbO2 of the healthy zone ZS and of the zone to be characterized ZC, as a function of the difference or differences between the determined values ​​of the diffusion coefficient ps of the zone 22 healthy ZS and the zone to be characterized ZC and depending on the difference(s) between the determined values ​​of the absorption coefficient pa of the healthy ZS zone and the zone to be characterized ZC. According to this second embodiment, the IND indicator, calculated during step 140 using the second calculation software 40, is a function of the concentration of the or each chromophore HbO2, Hb previously calculated, of the or each determined value of the diffusion coefficient ps of the zone to be characterized ZC and also of the or each determined value of the absorption coefficient pa of the zone to be characterized ZC. The quantification indicator IND is preferably calculated as a function of an average, such as the arithmetic average, of a plurality of values ​​of the diffusion coefficient ps of the zone to be characterized ZC, these values ​​of the diffusion coefficient ps being determined for a plurality of values ​​of the wavelength λ, for example between 450 nm and 800 nm, preferably between 650 nm and 800 nm, more preferably between 740 nm and 760 nm. The quantification indicator IND is also preferably calculated as a function of an average, such as the arithmetic average, of a plurality of values ​​of the absorption coefficient pa of the zone to be characterized ZC, these values ​​of the absorption coefficient pa being determined for a plurality of values ​​of the wavelength of the light beam, for example between 450 nm and 800 nm, preferably between 450 nm and 700 nm, more preferably between 500 nm and 650 nm. The quantification indicator IND then verifies, for example, the following equation: IND = a2 + p2 x Ox + y2 x Deox + ô2 x Dif + e2 x Abs (24) where IND represents the quantification indicator of the dermal reaction, a2, P2, Y2, ô2 and e2 are predetermined coefficients for a given value of the delay between the instant of measurement of the spectrum M of the backscattered radiation and the instant of injection of the active principle, with p2, y2, ô2 and e2 of non-zero values, Dif represents the average, such as the arithmetic mean, of the determined value(s) of the diffusion coefficient ps calculated for the wavelength intervals indicated above, namely [450 nm; 800 nm], preferably [650 nm; 800 nm], and more preferably [740 nm; 760 nm], and Abs represents the average, such as the arithmetic mean, of the determined value(s) of the absorption coefficient pa calculated for the wavelength intervals indicated above, namely [450 nm; 800 nm], preferably [450 nm; 700 nm], and more preferably [500 nm; 650 nm]. The values ​​of the coefficients a2, p2, Y2, ô2 and e2 are, for example, predetermined empirically from tests carried out on a set of patients. This predetermination is preferably done via a discriminant factor analysis. Alternatively, the predetermination is preferably done via a principal component analysis. Alternatively, the quantification indicator IND is calculated as a function of a difference between the concentrations of the or each chromophore Hb, HbO2 of the healthy zone ZS and the zone to be characterized ZC, as a function of the difference(s) between the determined values ​​of the diffusion coefficient ps of the healthy zone ZS and the zone to be characterized ZC and as a function of the difference(s) between the determined values ​​of the absorption coefficient pa of the healthy zone ZS and the zone to be characterized ZC. According to this variant, the quantification indicator IND then verifies, for example, the following equation: IND = a'2 + P'2 x AOx + Y'2 x ADeox + ô'2 x ADif + e'2 x AAbs (25) where IND represents the dermal reaction quantification indicator, a'2, P'2, Y'2, 5'2 and e'2 are predetermined coefficients for a given value of the delay between the instant of measurement of the spectrum of a backscattered radiation and the instant of injection of the active principle, with P'2, Y'2 and ô'2 of non-zero values, AOx and ADeox represent a difference between the oxyhemoglobin HbO2 concentrations of the healthy zone ZS and the zone to be characterized ZC, and respectively a difference between the deoxyhemoglobin Hb concentrations of the healthy zone ZS and the zone to be characterized ZC, and ADif and AAbs represent an average, such as the arithmetic mean, of the deviation(s) between the determined values ​​of the diffusion coefficient ps of the healthy zone ZS and the zone to be characterized ZC, and respectively of the deviation(s) between the determined values ​​of the absorption coefficient pa of the healthy zone ZS and the zone to be characterized ZC. The average to obtain ADif is, for example, calculated for the wavelength intervals indicated above, namely [450 nm; 800 nm], preferably [650 nm; 800 nm], and more preferably [740 nm; 760 nm], and that to obtain AAbs is, for example, calculated for the aforementioned wavelength intervals, namely [450 nm; 800 nm], preferably [450 nm; 700 nm], and more preferably [500 nm; 650 nm]. Similarly, the values ​​of the coefficients a'2, P'2, Y'2, 5'2 and e'2 are, for example, predetermined empirically from tests carried out on a set of patients. For example, the values ​​of the coefficients a2, p2, Y2, ô2 and e2 are respectively equal to 1.841, -0.128, -0.181, -0.463 and 0.324, as will be described later for equation (26) below. The results obtained with the method according to the second embodiment of the invention for the same group of 48 tests, as that indicated for the preceding figures 7 and 8, are illustrated on the histogram of figure 9 representing in the form of bars 550 the values ​​of the quantification indicator IND calculated for each of said 48 patients, also identified by respective numbers varying on the abscissa from 1 to 48. The results of figure 9 correspond to the case where the quantification indicator IND is calculated according to equation (25). In the example of figure 9, the quantification indicator IND verifies the following equation: IND = 1.841 - 0.128 xOx-0.181 x Deox - 0.463 x Dif + 0.324 x Abs (26) It is then noted that the number of diagnostic errors is even lower with the method according to the second embodiment than with the method according to the first embodiment, and a fortiori than with the method of the state of the art. Indeed, in the example of figure 9, only 4 errors are counted for 48 patients, i.e. an error rate equal to 8%, that is to say approximately 5.5 times less than the error rate of the state of the art. The errors are, in this example, 3 cases of false positive, the bars then being referenced 550A, and 1 case of false negative, said bar being referenced 550B. In the example of Figures 7 and 9, the IND quantification indicators are calculated 72 hours after the stimulation causing the dermal reaction. It was also found that it is possible to calculate the quantification indicator IND in a time significantly shorter than 72 hours using the calculation method according to the second embodiment, while maintaining a low error rate. Thus, sufficiently reliable indicators could be established, allowing earlier quantification of the reaction, the time between injection and reading being able to be reduced to 18 hours. It was further found that the results obtained are better when the quantification indicator IND is calculated from equation (25), rather than from equation (24). It is then understood that the method and the calculation system 10 according to the second embodiment of the invention make it possible to further improve the relevance of the calculated quantification indicator IND, while making it possible to calculate this indicator IND more quickly after the stimulation at the origin of the dermal reaction.

Claims

125 CLAIMS 1.-Method for calculating a quantification indicator (IND) of a dermal reaction of the skin (12) of a living being, such as a dermal reaction following the injection 5 of an active principle, the skin (12) comprising a plurality of chromophores (HbO2, Hb, Mel, Bil), the method comprising the following steps: - the illumination (100) of an area to be characterized (ZC) of the skin (12) via an excitation light beam emitted by a light source (14), the area to be characterized (ZC) 10 comprising the dermal reaction, - the measurement (110), using a spectrometer (16), of the spectrum (M) of backscattered radiation from the skin (12) following the illumination of said area to be characterized (ZC), - the determination (120), from the measured spectrum (M) and for at least one given value of the wavelength (X) of the light beam, of a value of the absorption coefficient (pa) of the zone to be characterized, - the calculation (130), from the or each determined value of the absorption coefficient (pa), of the concentration (Ox, Deox) of at least one chromophore (HbO2, Hb) of the skin, and 20 - the calculation (140) of the dermal reaction quantification indicator (IND) in function of the concentration of the or each chromophore previously calculated (Ox, Deox; AOx, ADeox), the method being characterized in that it further comprises the determination (120), from the measured spectrum (M) and for at least one given value of the wavelength 25 (A) of the light beam, of a value of the diffusion coefficient (ps) of the zone to be characterize, in that the dermal reaction quantification indicator (IND) is calculated also as a function of the or each determined value of the diffusion coefficient (ps, Dif; ADif), and 30 in that the dermal reaction quantification indicator (IND) verifies the following equation: IND = a + px Ox + yx Deox + 5 x Dif + ex Abs where IND represents the dermal reaction quantification indicator, a, p, y, 6 and e are predetermined coefficients for a given value of the delay 35 between the time of measurement of the spectrum of backscattered radiation and the time of injection of the active principle, with p, y. 6 and e of non-zero values, Ox and Deox represent the concentration of oxyhemoglobin (HbO2) and respectively of deoxyhemoglobin (Hb), for the zone to be characterized (ZC), Dif and Abs represent an average, such as the arithmetic mean, of the determined value(s) of the diffusion coefficient (ps) of the zone to be characterized (ZC), and respectively of the determined value(s) of the absorption coefficient (pa) of the zone to be characterized (ZC). 2.-Method for calculating a quantification indicator (IND) of a dermal reaction of the skin (12) of a living being, such as a dermal reaction following the injection of an active principle, the skin (12) comprising a plurality of chromophores (HbO2, Hb, Mel, Bil), the method comprising the following steps: - the illumination (100) of a zone to be characterized (ZC) of the skin (12) via an excitation light beam emitted by a light source (14), the zone to be characterized (ZC) comprising the dermal reaction, - the measurement (110), using a spectrometer (16), of the spectrum (M) of backscattered radiation from the skin (12) following the illumination of said area to be characterized (ZC), - the determination (120), from the measured spectrum (M) and for at least one given value of the wavelength (A) of the light beam, of a value of the absorption coefficient (pa) of the zone to be characterized, - the calculation (130), from the or each determined value of the absorption coefficient (pa), of the concentration (Ox, Deox) of at least one chromophore (HbO2, Hb) of the skin, and - the calculation (140) of the dermal reaction quantification indicator (IND) as a function of the concentration of the or each chromophore previously calculated (Ox, Deox; AOx, ADeox), the method being characterized in that it further comprises the determination (120), from the measured spectrum (M) and for at least one given value of the wavelength (A) of the light beam, of a value of the diffusion coefficient (ps) of the area to be characterized, in that the dermal reaction quantification indicator (IND) is calculated also as a function of the or each determined value of the diffusion coefficient (ps, Dif; ADif), during step (130) of calculating the concentration of the chromophore(s) (HbO2, Hb), the concentration of the chromophore(s) is further calculated for a healthy zone (ZS) of the skin (12) from the value(s) of the absorption coefficient (pa) for said healthy area (ZS), and during the calculation step (140), the dermal reaction quantification indicator (IND) is calculated as a function of a difference (AOx, ADeox) between the concentrations of the or each chromophore (Hb, HbO2) of the healthy zone (ZS) and of the zone to be characterized (ZC) and as a function of the difference(s) (ADif) between the determined values ​​of the diffusion coefficient (ps) of the healthy zone (ZS) and of the zone to be characterized (ZC), and furthermore as a function of the difference(s) (AAbs) between the determined values ​​of the absorption coefficient (pa) for a healthy zone (ZS) of the skin (12) and the zone to be characterized 10 (ZC), and The dermal reaction quantification indicator (IND) verifies the following equation: IND = a' + p' x AOx + y' x ADeox + ô' x ADif + £' x AAbs where IND represents the dermal reaction quantification indicator, 15 a', p', y', 5' and £' are predetermined coefficients for a given value of the delay between the time of measurement of the spectrum of backscattered radiation and the time of injection of the active principle, with P', y', 5' and e' of non-zero values, AOx and ADeox represent a difference between the oxyhemoglobin (HbO2) concentrations of the healthy zone (ZS) and the zone to be characterized (ZC), and respectively a difference 20 between the deoxyhemoglobin (Hb) concentrations of the healthy zone (ZS) and the zone to be characterized (ZC), ADif and AAbs represent an average, such as the arithmetic mean, of the deviation(s) between the determined values ​​of the diffusion coefficient (ps) of the healthy zone (ZS) and the zone to be characterized (ZC), and respectively of the deviation(s) between the 25 determined values ​​of the absorption coefficient (pa) of the healthy zone (ZS) and the zone to be characterized (ZC). 3.- Method according to claim 1 or 2, in which, during the calculation step (140), the indicator of quantification of the dermal reaction (IND) is calculated as a function 30 in addition of the or each determined value of the absorption coefficient (pa, Abs; AAbs). 4.- Method according to claim 3, in which the indicator of quantification of the dermal reaction (IND) is calculated according to an average (Abs; AAbs), such as the arithmetic average, of a plurality of values ​​of the absorption coefficient (pa), 35 determined for a plurality of values ​​of the wavelength (A) of the light beam 28 between 450 nm and 800 nm, preferably between 450 nm and 700 nm, more preferably between 500 nm and 650 nm. 5.-Method according to any one of the preceding claims, in which 5 the dermal reaction quantification indicator (IND) is calculated as a function of an average (Dif; âDif), such as the arithmetic average, of a plurality of values ​​of the diffusion coefficient (ps), determined for a plurality of values ​​of the wavelength (À) of the light beam between 450 nm and 800 nm, preferably between 650 nm and 800 nm, more preferably between 740 nm and 760 10 nm. 6.- Method according to any one of the preceding claims, in which the area (ZS, ZC) of the skin (12) is illuminated via an excitation optical fiber (24), and the measurement of the spectrum is carried out via a plurality of detection optical fibers (26) 15 connected to the spectrometer (16), the detection fibers (26) being at different distances (Dj) from the excitation fiber (24), and in which the determination, for at least one given value of the wavelength (A) of the light beam, of the value of the absorption coefficient (pa), respectively of the diffusion coefficient (ps), is carried out as a function of the spectra (M) 20 measured for said different distances (D,). 7.- Method according to any one of the preceding claims, in which the method further comprises the predetermination of a reference table (LUT) comprising a plurality of values ​​(RLut) of the reflectance of the skin, each value 25 (Rlut) of said table being predetermined for a respective pair of values ​​of the absorption coefficient (pa) and of the diffusion coefficient (ps), in which at least one value (RmeSure) of the reflectance of the zone to be characterized is measured using the spectrometer (16) during the measurement step (110), and in which during the step (120) of determining the absorption coefficient (pa) and of the diffusion coefficient (ps), the pair 30 of determined values ​​of the absorption coefficient (pa) and of the diffusion coefficient (ps) is that minimizing the error between the predetermined reflectances (Rlut)-of the reference table (LUT) and the measured reflectance value(s) (R^esure). 8.- Method according to claim 7, in which the area (ZS, ZC) of the skin (12) 35 is illuminated via an excitation optical fiber (24), and the measurement of the spectrum is carried out via a plurality of detection optical fibers (26) connected to the spectrometer (16), the 29 detection fibers (26) being at different distances (Di) from the excitation fiber (24), and wherein the predetermination of the reference table (LUT) is carried out for said different distances (DJ), each value (Rlut.di) of said table being predetermined for a respective pair of values ​​of the absorption coefficient (pa) and of the diffusion coefficient (ps) and for said different distances (DJ, at least one value (Rmesure,Di) of the reflectance of the zone to be characterized being measured for each of said distances (DJ and using the spectrometer (16) during the measurement step (110). 9.- Method according to any one of the preceding claims, wherein, during the step (120) of calculating the concentration of the chromophore(s) (HbO2, Hb), the concentration of the chromophore(s) is first calculated for a healthy area (ZS) of the skin (12) from the value(s) of the absorption coefficient (pa) for said healthy area (ZS), and the concentration of the chromophore(s) (HbO2, Hb) is then calculated for the area to be characterized (ZC) from the concentration of the chromophore(s) for the healthy area (ZS) and the value(s) of the absorption coefficient (pa) for said area to be characterized (ZC). 10.- Method according to any one of the preceding claims, in which the or each chromophore is chosen from the group consisting of: water, melanin, oxyhemoglobin, deoxyhemoglobin and bilirubin, the oxyhemoglobin concentration (HbO2) and the deoxyhemoglobin concentration (Hb) being preferably calculated. 11.- System (10) for calculating an indicator (IND) for quantifying a dermal reaction of the skin (12) of a living being, such as a dermal reaction following the injection of an active principle, the skin (12) comprising a plurality of chromophores (HbO2, Hb, Mel, Bil), the system (10) comprising: - a light source (14) capable of emitting an excitation light beam to illuminate an area to be characterized (ZC) of the skin (12), said area to be characterized (ZC) comprising the dermal reaction, - a spectrometer (16) capable of measuring the spectrum (M) of backscattered radiation from the skin (12) following illumination of said area to be characterized (ZC), - an information processing unit (18) comprising: + first means (34) of determination, from the measured spectrum (M) and for at least one given value of the wavelength (λ) of the beam 30 luminous, of a value of the absorption coefficient (pa) of the zone to be characterized (ZC), + first calculation means (38) for calculating, from the or each determined value of the absorption coefficient (pa), the concentration of at least one chromophore (HbO2, Hb) of the skin, and + second calculation means (40) for calculating the dermal reaction quantification indicator (IND) as a function of the concentration of the or each chromophore (HbO2, Hb) previously calculated, characterized in that the first determination means (34) are further capable of determining, from the measured spectrum (M) and for at least one given value of the wavelength (A) of the light beam, a value of the diffusion coefficient (p3) of the zone to be characterized (ZC), and in that the second calculation means (40) are suitable for calculating the dermal reaction quantification indicator (IND) also as a function of the or each determined value of the diffusion coefficient (ps), the dermal reaction quantification indicator (IND) verifying the following equation: IND = a + px Ox + yx Deox + 5 x Dif + ex Abs where IND represents the dermal reaction quantification indicator, a, p, y, 5 and £ are predetermined coefficients for a given value of the delay between the instant of measurement of the spectrum of a backscattered radiation and the instant of injection of the active principle, with p, y, 5 and £ of non-zero values, Ox and Deox represent the concentration of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) respectively, for the area to be characterized (ZC), Dif and Abs represent an average, such as the arithmetic mean, of the determined value(s) of the diffusion coefficient (ps) of the zone to be characterized (ZC), and respectively of the determined value(s) of the absorption coefficient (pa) of the zone to be characterized (ZC). 12,-System (10) for calculating an indicator (IND) for quantifying a dermal reaction of the skin (12) of a living being, such as a dermal reaction following the injection of an active principle, the skin (12) comprising a plurality of chromophores (HbO2, Hb, Mel, Bil), the system (10) comprising: - a light source (14) capable of emitting an excitation light beam to illuminate an area to be characterized (ZC) of the skin (12), said area to be characterized (ZC) comprising the dermal reaction, - a spectrometer (16) capable of measuring the spectrum (M) of backscattered radiation from the skin (12) following illumination of said area to be characterized (ZC), - an information processing unit (18) comprising: + first means (34) for determining, from the measured spectrum (M) and for at least one given value of the wavelength (A) of the light beam, a value of the absorption coefficient (pa) of the zone to be characterized (ZC), + first calculation means (38) for calculating, from the or each determined value of the absorption coefficient (pa), the concentration of at least one chromophore (HbO2, Hb) of the skin, and + second calculation means (40) for calculating the dermal reaction quantification indicator (IND) as a function of the concentration of the or each chromophore (HbO2, Hb) previously calculated, characterized in that the first determination means (34) are further capable of determining, from the measured spectrum (M) and for at least one given value of the wavelength (A) of the light beam, a value of the diffusion coefficient (ps) of the zone to be characterized (ZC), and in that the second calculation means (40) are suitable for calculating the dermal reaction quantification indicator (IND) also as a function of the or each determined value of the diffusion coefficient (ps), the first calculation means (38) being further adapted to calculate the concentration of the chromophore(s) for a healthy zone (ZS) of the skin (12) from the value(s) of the absorption coefficient (pa) for said healthy zone (ZS), and the second calculation means (40) being further adapted to calculate the dermal reaction quantification indicator (IND) as a function of a difference (AOx, ADeox) between the concentrations of the or each chromophore (Hb, HbO2) of the healthy zone (ZS) and of the zone to be characterized (ZC), as a function of the difference(s) (ADif) between the determined values ​​of the diffusion coefficient (ps) of the healthy zone (ZS) and of the zone to be characterized (ZC), and further as a function of the difference(s) (AAbs) between the determined values ​​of the absorption coefficient (pa) for a healthy zone (ZS) of the skin (12) and of the zone to be characterized (ZC), the dermal reaction quantification indicator (IND) verifying the following equation: IND = a' + p' x AOx + y' x ADeox + 5' x ADif + e' x AAbs where IND represents the dermal reaction quantification indicator, a', P', y'. 6' and e' are predetermined coefficients for a given value of the delay between the instant of measurement of the spectrum of a backscattered radiation and the instant of injection of the active principle, with p', y', 5' and e' of non-zero values, AOx and ADeox represent a difference between the oxyhemoglobin 5 (HbO2) concentrations of the healthy zone (ZS) and the zone to be characterized (ZC), and respectively a difference between the deoxyhemoglobin (Hb) concentrations of the healthy zone (ZS) and the zone to be characterized (ZC), ADif and AAbs represent an average, such as the arithmetic mean, of the deviation(s) between the determined values ​​of the diffusion coefficient (p9) of the healthy zone 10 (ZS) and the zone to be characterized (ZC), and respectively of the deviation(s) between the determined values ​​of the absorption coefficient (pa) of the healthy zone (ZS) and the zone to be characterized (ZC).

Images